Diabetic foot ulcers are the leading cause of non-traumatic limb amputations in the United States, with approximately 73,000 cases annually (ref 1; incorporated by reference in its entirety). Approximately 25% of diabetics are at risk of developing foot ulcers, which can lead to frequent hospitalizations due to severe impairment of the wound healing process (ref 2; incorporated by reference in its entirety). Although the field of wound care and management is well-established, the treatment of diabetic foot ulcers still remains a challenge (ref 3; incorporated by reference in its entirety). This discrepancy stems from the fact that traditional wound care fails to address the issues associated with the impaired wound healing process in diabetic patients.
To resolve this problem, most academic and industrial efforts have focused on the release of a drug or protein to pharmacologically affect the wound and improve healing rates (refs. 3-18; incorporated by reference in their entireties). Efforts have also used auto-/allogeneic cells to recellularize skin tissue equivalents (refs. 19-21; incorporated by reference in their entireties). Although with some promising data, there are substantial hurdles that a drug, protein releasing system and cell-based system must overcome from a regulatory standpoint, including dosing and the safety and efficiency studies, which lead to delayed development time and high costs. Frequent reapplication is often required due to lack of sustained release capabilities for many of the materials reported in the literature. Furthermore, there are often side effects that are only found with general patient use and can hinder the widespread use of the product as is the case with Regranex (becalpermin) which increases the risk of cancer (refs. 22-24; incorporated by reference in their entireties). Skin equivalents, on the other hand, normally end up being costly with limited shelf life due to incorporation of live cells (refs. 25, 26; incorporated by reference in their entireties). The transplanted cells with in those scaffolds also have been shown to have questionable survival rate on the wound bed according to several studies (ref 27, 28; incorporated by reference in their entireties). What is needed are materials and wound dressings that overcome these existing obstacles and address the issue of wound care, particularly for diabetic patients.